Ulcerative colitis (UC) is a complex disease that results from a dysregulated immune response in the gastrointestinal tract. A mouse model orally administered with dextran sodium sulfate (DSS) is the most widely used experimental animal model of UC. However, the ultrastructure of the colon in mouse colitis is poorly understood. In the present study, colonic specimens from DSS-induced UC mice underwent hematoxylin and eosin staining, Masson's trichrome staining and Verhoeff's elastic staining. In addition, the ultrastructure of samples was examined by transmission electron microscopy. UC was successfully induced by 7 consecutive days of DSS oral administration. The goblet cell architecture of the UC tissue was damaged in the mucosa. Additionally, a significant number of inflammatory cells infiltrated into the stroma and the structure of the intestinal gland was destroyed. The tissue in the submucosa showed significant edema. Hyperplasia was also identified in the submucosa, promoting a disorganized microstructure within the colon wall. Numerous collagen fibers in the muscular layer were disrupted, and the fiber bundles were thinner compared with those in the normal control group. Furthermore, in the DSS-induced UC group, the smooth muscle cell showed edema, the cell membrane structure was unclear and the shape of the nucleus was irregular. In conclusion, the present study revealed important histological and ultrastructural changes in the colon of DSS-induced UC mice. These features may contribute to improved understanding of the pathogenesis and mechanism of UC.